Freezing and thawing vessel with thermal bridge formed between internal structure and heat exchange member

ABSTRACT

The present invention relates to a thermal transfer system for heating or cooling a medium. A structure positioned inside a container. The structure segments the container into a plurality of compartments wherein a distal end of the structure is in close proximity to an interior surface of the container to allow formation of a thermal transfer bridge that conducts heat into or out of the medium.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. patent applicationSer. No. 09/895,777 filed on Jul. 17, 1997, which claims the benefit ofProvisional Application Serial No. 60/1037,283, filed Feb. 4, 1997. Thepresent application is related to U.S. patent application Ser. No.08/895,836, filed Jul. 17, 1997. All applications being herebyincorporated by reference as if repeated herein in its entirety,including the drawings.

FIELD OF THE INVENTION

[0002] The present invention relates generally to systems containingstructures such as fins to aid in the transfer of heat into or out of amedium. More particularly, the present invention relates to heating andcooling structures which are suited for use in heat, cooling, thawing,and freezing biopharmaceutical products.

DESCRIPTION OF THE PRIOR ART

[0003] Typically, a container used to heat or cool a medium will have aheat exchange fluid circulated in tubes placed in or around the exteriorof the container. In order to improve the transfer of heat to or fromthe medium to the heat exchange fluid, one or more extensions of thecontainer or any structures in the container may be used to increase thesurface area of the system that is in contact with the medium.

[0004] Ordinarily, fins will be attached by one end to a portion of thecontainer or some other structure in the container, and the fins willconduct heat to or from that portion of the container. However, since afin is typically attached to the container or an internal structure atonly one point, all of the heat transferred to or from the fin to thecontainer or an internal structure must enter or leave the fin throughthe one connection that the fin has with the rest of the system.

[0005] One configuration that has been used to solve this problem is tobuild a system in which one or more of the fins are rigidly attached toboth the container and an internal structure within the container. Thisallows heat to be transferred to or from a fin through two portions ofthe fin, increasing the rate at which heat is put into or withdrawn froma medium placed in the container.

[0006] However, by rigidly attaching a fin between the container and astructure within the container, the structure within the containeritself then becomes rigidly attached to the container. The rigidattachment of the structure inside the container can make cleaning anddecontaminating the container more difficult. Additionally, it may bemore difficult to manufacture the system because, for example, tightertolerances may be required so that the fin can be attached to twosurfaces within the container, and each fin may require two or morewelded joints. Furthermore, it may be inconvenient, costly, orimpossible for fins made of certain materials to be welded to acontainer.

[0007] What is needed is a system in which heat can be put into orwithdrawn from a fin through more than one portion of the fin while thesystem is operating while enabling structures within the container to beremoved to allow for cleaning and decontaminating of the system.Furthermore, what is needed is a system in which it is not required tophysically connect or weld the fin to a portion of the container inorder for heat to be transferred into or out of a portion of the fin.

SUMMARY OF THE INVENTION

[0008] It is an object of the present invention to have a system inwhich heat can be transferred into or out of a system through heatconduction pathways which are partially comprised of the medium beingheated or cooled such that heat flows between different portions of thesystem by flowing through the medium.

[0009] It is an object of the present invention to have a system inwhich heat can be transferred into or out of a structure within thecontainer (e.g. a fin) through more than one portion of the structure.(The term “fin” will be used generically to mean any heat exchangemember of the system that extends into the medium, including but notlimited to a coil, a flattened protrusion, a tube, or any otherstructure extending into the container. Where a particular type ofextension of the container is being discussed, such as a coil, the nameof the particular type of extension may be used to help clarify theconfiguration of the system.)

[0010] It is a further object of the present invention to have a systemin which structures within the container can be removed to allow forcleaning and decontaminating of the system.

[0011] It is yet a further object of the present invention to have finswhich contain passageways allowing cooling fluid to flow within thefins.

[0012] It is another object of the present invention to have fins whichenhance the removal of heat from a medium but which are not rigidlyattached to another portion of the system.

[0013] It is yet another object of the present invention to have finswhich have nonuniform cross-sections to allow from more rapid removal ofheat from a medium in the system.

[0014] It is still another object of the present invention to have asystem that achieves controlled freezing rates for a medium such as apharmaceutical product to aid in cryopreservation.

[0015] It is a yet another object of the present invention to have asystem which encourages a controlled freezing process to promotedendritic ice growth to aid in the cryopreservation of mediums includingbut not limited to proteins, cells, blood, plasma, otherbiopharmaceutical products, or food products.

[0016] It is a further object of the present invention to have a systemthat can rapidly heat or cool a medium.

[0017] These and other objects of the present invention are achieved bythe use of a structure positioned inside a container. The structuresegments the container into a plurality of compartments wherein a distalend of the structure is in close proximity to an interior surface of thecontainer to allow formation of a thermal transfer bridge that conductsheat into or out of the medium.

[0018] In one embodiment of the present invention, the structureincludes a fin. A distal end of the fin is placed in close proximity toa portion of the container. Since the fin, and the container are notrigidly attached the structure, including the fin, can be removed fromthe container.

[0019] When a medium inside the container is frozen, a bridge made ofthe frozen medium will form between the distal end of the fin and theportion of the container close to the distal end of the fin. This bridgewill allow heat to be conducted to or from the fin across the bridgespeeding the removal of heat from the medium.

[0020] In one embodiment of the present invention, the fin is at leastpartially attached to a structure within the container allowing heat tobe transferred out of the fin through the attachment point and thethermal bridge when it is formed.

[0021] In another embodiment of the present invention, the distal end ofthe fin is placed close enough to another surface of the container, forexample, another fin or structure in the container, such that when themedium is cooled, the thermal transport bridge is formed between the finand the other structure in the container—which may of course be a fin.

[0022] The present invention is useful for both the cooling and heatingof a medium. When a medium is being frozen the thermal bridges helptransfer heat out of the medium. When the medium is being heated thethermal bridges help heat to be transferred into the medium.

[0023] The medium can also be a gas being converted to a liquid or aliquid being converted to a gas. In these cases the liquid phase of themedium that collects between the fin and the structure will act as thethermal bridge to enhance the conduction of heat between the fin and thestructure.

[0024] Additionally, the fin can have structures on it which willenhance the formation of solid or liquid thermal bridges and/or enhancethe heat conduction through such bridges. For example, a portion of thefin may be enlarged to provide more surface area for conduction andcontact with a thermal bridge, or the fin may be tailored to enhancenucleation of the solid or condensation of the liquid. Also, a fin mayhave a non-uniform cross-section to enhance thermal transport or achievedesired thermal transport characteristics. This may be desirable to helpachieve cryobiology protocols. Furthermore, the fin can have interiorchannels that allow a heat exchange medium to flow within at least aportion of the fin. Other variations are possible without departing fromthe spirit of the invention.

[0025] The system may be configured so that a heating or cooling deviceis coupled to any portion of the container. For example, withoutdeparting from the present invention, a heater or cooler could beattached to an exterior portion of the container (e.g. a wall of thecontainer), to an internal structure of the container, or directly toone or more of the fins.

[0026] In general, the system should be constructed such that thedistance to be bridged by the thermal transport bridge will be afunction of the thermal properties of the medium and the system,manufacturing requirements and construction processes used to build thesystem, and other relevant parameters of the system and components used.The size of the gap to be filled by the bridge can be determined throughsimple trial and error, and the optimum gap may be no gap.

[0027] In one aspect of the present invention, the fins may bestructures of any shape which are placed against or wedged betweensurfaces in the container. Thermal bridges will then form between thefins and the adjacent surface or surfaces of the container. For example,the fins can have ends adapted to fit in preconfigured slots in surfacesof the container. In this way the fins can be reconfigurable attached toportions of the container so that the number, configuration, and type ofthe fins used can be easily changed to meet changing manufacturing,process, or protocol needs.

[0028] In one aspect of the present invention, the optimum gap isproportional to the thickness of the fin. In another aspect of thepresent invention, the optimum gap is less than 2 inches, preferablyless than 1 inch, more preferably less than ½ inch, even more preferablyless than ¼ inch, and most preferably less than ⅛ inch.

[0029] Without departing from the present invention, the container canbe porous and need not have a top or a bottom. The medium can be heatedor cooled as it passes through the container. Additionally, thecontainer used in the present invention is not limited in shape, size ormaterial from which it is constructed. In one aspect of the presentinvention, the container may have a volume of 1 liter to 5 liters, 1liter to 250 liters, or 250 to 10,000 liters.

[0030] The present invention can be usefully applied in many fields. Forexample in the biopharmaceutical industry the present invention can beused to freeze and preserve a variety of biopharmaceutical products,including but not limited to proteins, cells, antibodies, medicines,plasma, blood, buffer solutions, viruses, serum, cell fragments,cellular components, and any other biopharmaceutical product.

[0031] Additionally, the present invention allows processing of suchbiopharmaceutical products consistent with generally acceptedmanufacturing procedures.

[0032] One could use the present invention to freeze a biopharmaceuticalproduct by sterilizing the container, pumping the product to be frozeninto the container through a sterile filter and then removing heat fromthe product using the present invention to freeze the product within thecontainer.

[0033] The present invention promotes uniform freezing at a rapid pacewhich allows the product in the container to be frozen in as close toits native state as possible. Additionally, the present invention allowsthe freezing process to be done in a repeatable fashion so that a usercan be assured that the freezing process is not causing batch to batchvariations in the product. This allows the end use of the product to bedecoupled from the manufacturing steps needed to create the productsince the product can be stored in the frozen state after it ismanufactured, and thawed when and where it is needed.

[0034] The present invention can also be used during any stage of apurification process. For example, after products are processed usingsize separation or affinity separation, fermentation, licing,concentration filtration, selective affinity chromatography, removal ofmicro contaminants or low level impurities through ion exchange, viralfiltration, chromatography, putting the product in a buffered solutiondelivery system, or after any other processing step the resultingproduct can be stored using the present invention. This allows a hold tobe put on the manufacturing process without degrading the intermediateproduct.

[0035] For example, if during a manufacturing process in which variouscomponents are being separated, one wishes to put a hold on theprocessing, there may be contaminating proteaises in the intermediateproduct which may, over time, degrade some of the proteins of interestin the product. The present invention can be used to freeze theintermediate product quickly and uniformly enough so that the productremains close to its native state. The molecules in the product are notbrought significantly closer together—freeze concentration is reduced,and unwanted reactions can be slowed or stopped.

[0036] Thus, the present invention can be used to increase theflexibility of a manufacturing process, making planning and schedulingof the process easier. Intermediate products can be frozen for laterprocessing or shipping. Additionally, since the present invention can bescaled to any size desired, large batches of products can be preparedall at once, preserved using the present invention, and used as neededat a later time.

BRIEF DESCRIPTION OF THE DRAWINGS

[0037]FIG. 1 is a side view of the finned heating and cooling apparatus.

[0038]FIG. 2 is a top view of the fins and the structure within thecontainer depicted in FIG. 1.

[0039]FIG. 3 depicts the formation of thermal bridges and graphs showingthe temperature profile of various cross-sections of the container andmedium.

[0040]FIG. 4 is another possible arrangement of the fins.

[0041]FIG. 5 is yet another possible arrangement of the fins.

[0042]FIG. 6 depicts a number of possible fin geometries andcombinations.

[0043]FIG. 7 depicts yet more possible fin geometries and combinations.

[0044]FIG. 8 depicts still another possible configuration of fingeometries and combinations.

[0045]FIG. 9 depicts a cross-sectional view of a fin showing anon-uniform thickness.

[0046]FIG. 10 depicts a fins geometry which allows compartmentalizationof the container through the use of alternate fin geometries.

[0047]FIG. 11 is a cutaway view showing a container and the interiorbaffles of two fins.

[0048]FIG. 12a is a top view of the container and fins of FIG. 11.

[0049]FIG. 12b is a detail view of the distal end of a fin with anextension extending close to the interior wall of the container.

[0050]FIG. 12c is a detail view showing another embodiment of a finwithout an extension in which the hollow fins structure extends close tothe interior wall of the container.

[0051]FIG. 13 is a cutaway view showing a container, the interiorbaffles of two fins, and no central structure. The heat exchange fluidis fed into the fins through tubes in the top of the fins.

[0052]FIG. 14a is a cutaway view showing a container, a set of interiorfins, a set of exterior fins and a coil.

[0053]FIG. 14b is a top view of the system of FIG. 14a.

[0054]FIG. 15a is a cutaway view showing a container, a set of interiorfins, a set of middle fins, a set of exterior fins, a first coil, and asecond coil.

[0055]FIG. 15b is a top view of the system of FIG. 15a.

[0056]FIG. 15c is a detailed side view of the thermal bridges that formbetween each of the winds of the coils and between the fins and thewinds of the coils.

[0057]FIG. 15d is a detailed top view of the thermal bridges that formbetween the coils and the fins.

[0058]FIG. 16 depicts non-circular cross-section tubes.

[0059]FIG. 17 depict non-circular cross-section tubes in use in asystem.

[0060]FIG. 18 depict non-circular cross-section tubes attached to finsin various configurations.

[0061]FIG. 19 depict non-circular cross-section tubes in use in a coilconfiguration within a system.

[0062]FIG. 20 depicts a configuration of non-circular cross-sectiontubes and fins useful for compartmentalizing a system.

DETAILED DESCRIPTION

[0063] One embodiment of the present invention is shown in FIG. 1.Heating and cooling system 2 is comprised of container 4, fins 6 andstructure 8. Fins 6 are configured such that they are placed in closeproximity to interior surface 10 of container 4. Generally, a small gapbetween fin 6 and interior surface 10 is preferable. However, the sizeof this gap may be dictated by manufacturing tolerances, materialparameters, or other practical considerations.

[0064]FIG. 2 shows a cutaway top view of container 4, fins 6 andstructure 8. In the present embodiment there are 6 fins placedsymmetrically about structure 8. Any arrangement design, configuration,or number of fins could be used without departing from the presentinvention. For example, the fins need not be symmetrically positionedwithin the container, they need not be the same shape and they need notbe made of the same material.

[0065] Referring again to FIG. 1, structure 8 is heated or cooled byflowing a heat exchange fluid down interior passage 12 towards end piece14. The heat exchange fluid then flows up through the outer passage 16of structure 8. This flow pattern of the heat exchange fluid and thesymmetric configuration of the fins about structure 8 aids system 2 tobegin cooling the medium in the container from the bottom up. This is sobecause the heat exchange fluid is first closely coupled to the mediumin the container and the fins at the bottom of the container.

[0066] Cooling the medium from the bottom up is particularlyadvantageous when a liquid medium is being frozen and, as is true forwater, the density of the frozen medium is less than that if the liquidphase. Freezing from the bottom up prevents pressure from building up asmight be the case if the liquid phase was constrained by the solidphase.

[0067] It should be appreciated that one skilled in the art could useother flow patterns, fin shapes, and fin configurations to induce themedium to heat or cool in any preferred direction, uniformly, and/or ata specified rate without departing from the present invention.Additionally, parameters of the heat exchange fluid such as flow rateand/or temperature can be used to affect the rate at which the medium iscooled.

[0068] End piece 14 has bottom fin 30 attached to it. Bottom fin 30functions the same as fins 6. A thermal transport bridge is formedbetween bottom fin 30 and a portion of interior surface 10.

[0069] In one aspect of the present invention, taper 19 on fin 6 helpsto slow the formation of a thermal bridge on the upper portion of fin 6.This will slightly slow the heat transfer out of the upper portion ofthe container, allowing the system to freeze the medium from the bottomup. Such a taper can be used on any portion of the fin to help create apreferred direction for removal of heat from the container.

[0070] Container 4 has jacket 20 surrounding its circumference. Betweenexterior surface 18 of container 4 and jacket 20 is fluid flow path 22.Spiral baffle 24 corkscrews around container 4 between exterior surface18 and jacket 20 forcing heat exchange fluid in fluid flow path 22 toflow in a spiraling path around the exterior surface 18 of container 4.Heat exchange fluid flows into fluid flow path 22 through port 26 andout through port 28 resulting in the heat exchange fluid flowing aroundcontainer 4 from the bottom to the top. This flow pattern for the heatexchange fluid aids system 2 in cooling the medium in the container fromthe bottom up.

[0071] It should be appreciated that other fluid flow patterns andbaffles can be used to induce the medium to heat or cool in anypreferred direction, uniformly, and/or at a specified rate withoutdeparting from the present invention. Additionally, parameters of theheat exchange fluid such as flow rate and/or temperature can be used toaffect the rate at which the medium is cooled.

[0072] Furthermore, the heat exchange fluid can be flowed through thesystem at other points and in a time or process varying manner in orderto tailor the timing, direction, and rate of heat flow into or out ofthe system. Additionally, materials used in, or the shape, orconfiguration of the system, including the fins, can be used to controlparameters of the heating or cooling process such as rate, timing ordirectionality.

[0073] When container 4, structure 8 and fins 6 are cooled by thecoolant, the medium in the container begins to cool. When the medium issufficiently cooled, a portion of the medium between the distal end offins 6 and interior surface 10 will freeze. This frozen bridge willallow heat to be conducted between fins 6 and container 4 through thefrozen bridge. This will enable heat to be taken out of the medium at ahigher rate, speeding the freezing of the medium in the container. Thepresent invention will work with any type of medium including but notlimited to biopharmaceutical products.

[0074]FIG. 3 illustrates the formation of thermal bridges in accordancewith one aspect of the present invention. FIG. 3a is a top view of oneembodiment of the present invention in which structure 31 has 8 fins 32attached to it. Each fin 32 extends close to interior surface 33 ofcontainer 34.

[0075]FIG. 3b illustrates a simulation for the system shortly afterthermal bridges 35 have begun to form. In this simulation, the materialproperties of 315 stainless steel were used for the container and thefins, and the coolant temperature was −45 EC. The temperature of theliquid was −0.2 EC, the temperature of the fin in contact with theliquid was close to −0.2 EC, and the temperature of the portion of thefin in contact with the frozen product was declining toward thetemperature of the wall. The temperature of the wall was within 2-5 ECof the temperature of the coolant.

[0076] As can be seen from the graphs in FIG. 3b, heat is beingextracted from fins 32 through both ends. When compared to a finnedstructure in which heat is extracted form only one end of the fin, themedium will be cooled at a faster rate. FIG. 3c depicts the temperatureprofile of the medium within the compartments 36 formed by fins 32. Asshown in the graphs in FIG. 3c, heat is withdrawn from the medium withinthe cavity through interior container wall 33, structure 31 and fins 32.

[0077] The relative uniformity with which the present invention allowsheat to be removed from the medium promotes the growth of dendriticstructures during the freezing process. The present invention, byallowing heat to be removed from both ends of a fin, helps to create auniform temperature profile within the container.

[0078] Additionally, the fins can be positioned to effectively segmentthe container into a plurality of smaller volumes, so that heat can bemore uniformly removed from each segmented section. As an example, FIG.2 shows container 4 segmented into 6 section by the fins.

[0079] It is noted that the present invention can be used to achievedendritic ice growth even if fins are rigidly attached at more than onepoint to the system. Fins can be used to segment the container intosmall regions which can be more uniformly heated and cooled. Thus, if aparticular application does not require that the internal structures ofthe container be removable, the fins and structures can be permanentlyattached within the container.

[0080] Dendritic ice growth is particularly useful many areas, includingbut not limited to the cryopreservation of biopharmaceutical products.As shown in FIG. 3d, when heat is removed from surface 501 (which couldbe any surface of the present invention), dendrites 502 will form andgrow moving away form surface 501.

[0081] As dendrites 502 grow, the substance 503 in the medium beingfrozen and will eventually become surrounded by dendrites 502. Asdendrites 502 grow, substance 503 will eventually become trapped in thefrozen medium 504. By controlling the heat removal from surface 501, thegrowth rate of dendrites 502 can be controlled. Controlling the growthrate of dendrites 502 allows the present invention to be used to controlthe amount of liquid removed from substance 503 as it enters and becomestrapped by growing dendritic front 505. It is noted that substance 503can be any substance one desires to preserve.

[0082] It should be appreciated that there need not be active cooling ofboth the structure and the container to employ the present invention.Without departing from the present invention, coolant can be circulatedthrough any part of the system, only one part of the system, or coolantneed not be used and the system could be cooled by other means orindirectly or passively.

[0083] In another embodiment of the invention, removable liners can beplaced over the distal ends of fins 6 to prevent them from contactinginterior surface 10 when structure 8 and fins 6 are inserted or removedfrom container 4. This may be desired, for example, to avoid scratchinginterior surface 10 with fins 6 during assembly and disassembly.

[0084] Other fin configuration are possible without deviating from thepresent invention. For example, in FIG. 4, fins 39 may be partiallycoupled to interior container wall 41 and the distal end of each fin canbe place in close proximity to structure 37 such that the thermal bridgeis formed between a distal end of each of fins 39 and structure 37.

[0085] In FIG. 5, fins 40 are attached to interior surface 42. Fins 44are attached to structure 46. System 38 is constructed such thatportions of fins 40 and fins 44 are in contact, nearly in contact or canbe rotated such that this is the case. Then, when the medium in thecontainer freezes, thermal transport bridges will form between portionsof fins 40 and fins 44. In another aspect of this invention, fins 40 and44 need not be parallel. Fins 40 and 44 can be angled with respect toeach other such that gap 45 varies along the length of fins 40 and 44.

[0086]FIG. 6 depicts a number of possible arrangements of fins. Forexample, fin 48A may be partially coupled to structure 50A and a distalend placed in close proximity to another structure, 50B, such that thethermal bridge is formed between the distal end of fin 48A and structure50B Fins 54 are coupled to interior wall 56. A distal end of fin 54A isplaced near distal ends of fins 58, and fins 58 are coupled tostructures 50. A thermal bridge will form between the distal ends offins 54A, 58A and 58B. Thus, a thermal bridge can be formed between morethan two fins. Forming a thermal bridge between two or more fins may bedesirable if, for example, design constraints or other constraintsrequire portions of the container to be held a distance from an activelycooled surface. A fin and thermal bridge can be used to help extractheat from the isolated structure.

[0087]FIG. 7 depicts a number of other possible arrangements of fins. Afin can be configured so that the thermal bridge is formed not betweenthe distal ends of two fins but between the distal end of one fin andsome other portion of another fin. For example, fin 60 will form athermal bridge with fin 62 at a central portion of fin 60, and fin 64will form a thermal bridge with fin 66 at a central portion of fin 64.Furthermore, a fin need not be initially coupled to anything and thermaltransport bridges may be formed between portions of the fin and otherportion of the system. For example, fin 68 is not rigidly attached toany structure within the container, but it will form a thermal bridgewith fins 64 and 70 and structures 72.

[0088] Additionally, fins may have structures on them to aid in theformation of thermal transport bridges or to enhance the thermaltransport capabilities of the bridges. Fins 62 have extended surfaces 76on their distal ends. Extended surface 76 will allow a wider thermalbridge to be formed, improving the heat transfer rate of the bridge.This may be desirable in certain circumstances. For example, the thermaltransport properties of the fin material may be superior to those of thefrozen material that forms the thermal bridge. Increasing the area ofthe thermal bridge will improve its total heat transfer properties.

[0089] Additionally, other types of extended surfaces can be put onfins, the structures or the interior surface of the container to aid inthe formation of thermal transport bridges with the desired properties.For example, extended surface 78 may be used to enhance the formation ofa thermal bridge with fin 62 whether or not extended surface 76 isattached to fin 62.

[0090]FIG. 8 shows another embodiment of the present invention. Thisembodiment details another configuration of fins in accordance with thepresent invention. In this embodiment fins 80 are connected to structure81 and will form thermal bridges with structures 82. Fins 83 areconnected to structures 82 and will form thermal bridges with interiorcontainer wall 84. Fins 85 will form thermal bridges with each other,and fins 86 will form thermal bridges with interior container wall 84

[0091]FIG. 9 shows yet another embodiment of the present invention. Fin87 has a non-uniform cross section along its length. Fin 87 is thickerat end 88 where it connects to structure 89 and thinner in its centralportion. The fin then widens out at its distal end 90 where it is inclose proximity to interior surface 91 A thermal bridge will formbetween distal end 90 and interior surface 91. The thicker base of thefin will allow more heat flux to be withdrawn from the fin at end 88 anddistal end 90.

[0092]FIG. 10 shows still another embodiment of the present invention.Fins 92 are attached to structure 93 and will form thermal bridges withcontainer wall 94. Fins 92 are curved to form compartments 95.Compartmentalization of the container allows more uniform cooling to beachieved since the distance from any point in the medium to a cooledsurface is reduced. Also, the reduction in distance between cooledsurfaces can be used to decrease the time required to freeze a medium.Other fins such as fins 96 may be added to further compartmentalizecompartments 95. Fins 97 can also be used to form thermal bridges withanother structure 98. Those skilled in the art will realize that othershapes and configurations of fins can be used to create more or lesscompartments of any desired size, and that this scheme can be scaled toany desired container volume without departing from the presentinvention.

[0093]FIG. 11 shows another embodiment of the present invention. In thisembodiment fins 102 have interior passageways 104. Heat exchange fluidflows into interior passageways 104 through openings 106 in structure108. Fins 102 may have dimples 110 or spacers 114 or turbulizers to helpoptimize the flow pattern 118 of the heat exchange fluid. Dimples orspacers help optimize the flow pattern 118 of the heat exchange fluidfor reasons including, increasing the interior surface area of the finwhich comes in contact with the heat exchange fluid, and giving the heatexchange fluid more time to absorb heat from the fins. This speeds thefreezing process and allows converging of the dendrites more quickly.

[0094] In another aspect of the present invention, fins 102 may haveextensions 120 on them. As shown in FIG. 12a, heat exchange fluid doesnot flow within extensions 120. Extensions 120 are connected to fins 102and extend close to interior surface 122 of container 124. FIG. 12bshows a detail view of fin 102, extension 120 and interior surface 122.FIG. 12c shows a detail view of another embodiment of the presentinvention in which there is no extension placed on the end of fin 102.

[0095] As show in FIG. 12b, when the present invention is used to freezea medium within container 124, a thermal transfer bridge 126 will beginto form between interior surface 122 and extension 120. In FIG. 12c, thethermal transfer bridge will begin to form between fin 102 and interiorsurface 122.

[0096]FIG. 13 shows yet another embodiment of the present invention. Inthis embodiment the heat exchange fluid flows into and out of fins 202through tubes 204 connected to the top 206 of fins 202. In thisembodiment the fins are not connected to a central structure. When thisembodiment is used to freeze a medium, thermal transfer bridges 208 willform between the fins 202 and the interior surface 210 and betweeninterior portions 212 of fins 202.

[0097]FIG. 14a depicts yet another embodiment of the present invention.In this embodiment, system 300 has internal fins 304 which are attachedto structure 306. Heat exchange fluid flows through structure 306. Theflow of the heat exchange fluid can be configured to be similar to theflow described for structure 8 in FIG. 1. Any other flow configurationcan be used to achieve a desired cooling or heating rate. Additionally,heat exchange fluid may be flowed through interior fins 304 if desired.

[0098] Coil 308 is placed in a surrounding relationship to interior fins304. Heat exchange fluid flows into coil 308 through input 310 and flowsout through output 312. Exterior fins 314 are placed between coil 308and interior surface 316 of container 302. In one aspect of thisembodiment, exterior fins can be free standing, attached to coil 308 orattached to interior surface 316. In another aspect of this embodiment,heat exchange fluid can be flowed through exterior fins 314 through coil308, interior surface 316, external inputs, or any other supply.

[0099] In this embodiment, thermal transport bridges are formed betweeninterior fins 304 and coil 308, coil 308 and external fins 314, externalfins 314 and interior surface 316, and the coils of coil 308.

[0100]FIG. 14b show a top view of system 300. In this embodiment fins314 are depicted as not being attached to coil 308. Fins 314 could besuspended by supports from the top or bottom of container 302 or fins314 could be free standing.

[0101]FIG. 15 depicts still another embodiment of the present invention.In this embodiment system 400 has internal fins 402 attached tostructure 404 and first coil 406 surrounding internal fins 402. Middlefins 408 are placed around first coil 406 and second coil 410 surroundsmiddle fins 408. Exterior fins 412 are placed between second coil 410and interior surface 414. First and second coils 406 and 410 receiveheat exchange fluid through input 416 and 418 respectively and the heatexchange fluid flows out through outputs 420 and 422 respectively.

[0102]FIG. 15b shows a top view of this embodiment. In this embodimentfins 408 and 412 are depicted as freely suspended. Thermal transportbridges will form between internal fins 402 and first coil 406, thecoils of first coil 406, first coil 406 and middle fins 408, middle fins408 and second coil 410, the coils of second coil 410, second coil 410and exterior fins 412, and exterior fins 412 and interior surface 414.

[0103]FIG. 15c shows a detail side view of the formation of the thermaltransport bridges 424 between the coils of one of first coil 406 orsecond coil 410, and the thermal transport bridges 426 formed betweenthe coils and fins, interior fins middle fins or exterior fins.Distances X1 and X2 can be optimized as desired as a function of theproperties of the fins the coil the medium and the container. The FIG.15d shows a top view of the formation of the thermal bridges depicted inFIG. 15c.

[0104] FIGS. 16 show other possible configurations of coils consistentwith the present invention. In FIG. 16a, central pipe 602 has a roundcross section. Cooling fluid flows through the interior of pipe 602.Central pipe 602 is adjacent to and will form a thermal bridge with fin604. Pipe 606 also has cooling fluid flowing through it, and it isadjacent to the other end of fin 604. Pipe 606 has a non-circularcross-section. Any cross-section pipe can be used consistent with thepresent invention. In

[0105]FIG. 16b, a non-circular cross-section pipe 608 is show in adifferent orientation with respect to the adjacent fins.

[0106]FIG. 17 shows non-circular cross-section pipes used in a system.In FIG. 17a, the angle formed between two adjacent fins is small andtherefore the non-circular cross section pipes 610 are oriented so thatthey can be placed closer together. One advantage of using non-circularcross-section pipes is that the elongated surface area of non-circularpipes 610 allows for a longer portion of the interface betweencompartments 612 to be cooled by a pipe with a cooling medium flowingthrough it.

[0107]FIG. 17b shows non-circular cross-section pipe 614 used in adifferent 25 orientation from that in FIG. 17a. In FIG. 17b, the angleformed by adjacent fins is larger and therefore non-circularcross-section pipes 614 can be used in the orientation shown. In theorientation shown, non-circular cross-section pipes 614 protrude intothe adjacent compartments and advantageously help to more uniformly coolthe medium within the compartments.

[0108]FIG. 18 shows another configuration of pipes and fins that isconsistent with the present invention. In FIG. 18, the non-circularcross-section pipes 702 have fins 704 welded onto them.

[0109] FIGS. 19 show yet another example of the use of non-circularcross-section fins consistent with the present invention. In FIG. 19a anon-circular cross-section pipe 802 is wound into a coil, similar tocoil 308 of FIG. 14a. Non-circular cross-section pipe 802 has extendedflat side 804 adjacent to fins 806. Extended flat side 804 makes iteasier for thermal bridges to form between coil 808 formed by pipes 802and fins 806, and between pipes 802 of coil 808. FIG. 19b shows pipes810 of a different cross-section which also advantageously aid in theformation of thermal bridges.

[0110] Non-circular cross-section pipes 802 or 810 allow fins 806 orfins 812 to be closer together for a given internal pipe cross-sectionalarea when compared to a circular pipe. Since the fins are closertogether, thermal bridges will form more quickly, speeding up thefreezing process and keeping it more uniform.

[0111]FIG. 20 details yet another possible configuration of non-circularcross-section pipes 902 and fins 904. The geometry shown can be used tocompartmentalize large volume tanks. The compartments thus formed can bemade as small as is needed in order to achieve a desired level ofuniformity.

[0112] The present invention can be usefully applied in many fields. Forexample in the biopharmaceutical industry the present invention can beused to freeze and preserve a variety of biopharmaceutical products,including but not limited to proteins, cells, antibodies, medicines,plasma, blood, buffer solutions, viruses, serum, cell fragments,cellular components, and any other biopharmaceutical product.

[0113] Additionally, the present invention allows processing of suchbiopharmaceutical products consistent with generally acceptedmanufacturing procedures.

[0114] One could use the present invention to freeze a biopharmaceuticalproduct by sterilizing the container, pumping the product to be frozeninto the container through a sterile filter and then removing heat fromthe product using the present invention to freeze the product within thecontainer.

[0115] The present invention promotes uniform freezing at a rapid pacewhich allows the product in the container to be frozen in as close toits native state as possible. Additionally, the present invention allowsthe freezing process to be done in a repeatable fashion so that a usercan be assured that the freezing process is not causing batch to batchvariations in the product. This allows the end use of the product to bedecoupled from the manufacturing steps needed to create the productsince the product can be stored in the frozen state after it ismanufactured, and thawed when and where it is needed.

[0116] The present invention can also be used during any stage of apurification process. For example, after products are processed usingsize separation or affinity separation, fermentation, licing,concentration filtration, selective affinity chromatography, removal ofmicro contaminants or low level impurities through ion exchange, viralfiltration, chromatography, putting the product in a buffered solutiondelivery system, or after any other processing step the resultingproduct can be stored using the present invention. This allows a hold tobe put on the manufacturing process without degrading the intermediateproduct.

[0117] For example, if during a manufacturing process in which variouscomponents are being separated, one wishes to put a hold on theprocessing, there may be contaminating proteaises in the intermediateproduct which may, over time, degrade some of the proteins of interestin the product. The present invention can be used to freeze theintermediate product quickly and uniformly enough so that the productremains close to its native state. The molecules in the product are notbrought significantly closer together—freeze concentration is reduced,and unwanted reactions can be slowed or stopped.

[0118] These examples do not limit the present invention but are merelyexamples of possible embodiments of the present invention. Otherembodiments are possible without deviating form the present invention.

What is claimed is:
 1. A thermal transfer system, comprising: a container for receiving a medium; a structure positioned in the container such that the structure segments the container into a plurality of compartments wherein a distal end of the structure is in close proximity to an interior surface of the container to allow formation of a thermal transfer bridge that conducts heat into or out of the medium.
 2. A thermal transfer system as in claim 1 including: a heating or cooling device coupled to and provides heating or cooling of the container.
 3. A thermal transfer system as in claim 1 including: a heating or cooling device coupled to and provides heating or cooling of the structure.
 4. A thermal transfer system as in claim 1 including: a heating or cooling device coupled to and provides heating or cooling of the container and the structure.
 5. A thermal transfer system as in claim 1 including: a plurality of structures in the container.
 6. A thermal transfer system as in claim 1, including: a removable liner configured to cover at least a portion of the structure.
 7. A thermal transfer system as in claim 1 wherein: a volume of the container is in the range from substantially 1 liter to 250 liters.
 8. A thermal transfer system as in claim 1 wherein: a volume of the container is in the range from substantially 250 liter to 10,000 liters.
 9. A thermal transfer system as in claim 1 wherein: the distal end of the structure contacts at least a portion of the interior surface of the container.
 10. A thermal transfer system as in claim 1 wherein: a distance between the distal end of the structure and the interior surface of the container is a non-contacting distance not greater than one inch.
 11. A thermal transfer system as in claim 1 wherein: the container includes a jacket defining an interstitial space positioned between the jacket and a wall of the container for receiving a flow of a heat exchange fluid, the jacket further including a plurality of spiral baffles for enhancing thermal exchange between the heat exchange fluid and the container.
 12. A thermal transfer system as in claim 1 wherein: a heat exchange fluid flows within the structure.
 13. A thermal transfer system as in claim 12 wherein: an interior portion of the structure has baffles.
 14. A thermal transfer system as in claim 13 wherein: the structure is configured to maximize an area of a surface of the structure that is in contact with the medium.
 15. A thermal transfer system as in claim 12 wherein: a heat exchange extension is at least partially coupled to the structure.
 16. A thermal transfer system as in claim 1 wherein: the medium is substantially uniformly heated or cooled.
 17. A thermal transfer system as in claim 1 wherein: the medium is heated or cooled in substantially one direction relative to the structure.
 18. A thermal transfer system as in claim 1 wherein: the structure is positioned to induce a thermal gradient in the medium such that the thermal gradient is in a predetermined direction.
 19. A thermal transfer system as in claim 1 wherein: the medium is heated or cooled in a predetermined direction.
 20. A thermal transfer system as in claim 1 wherein: the medium is heated or cooled such that the thermal gradient is in a predetermined direction.
 21. A thermal transfer system as in claim 1 wherein: the medium is heated or cooled at a predetermined rate.
 22. A thermal transfer system as in claim 1 wherein: the medium is heated or cooled such that the thermal gradient is in a predetermined direction and the heating or cooling occurs at a predetermined rate.
 23. A thermal transfer system as in claim 1 wherein: the medium is a biopharmaceutical product.
 24. A thermal transfer system as in claim 1 wherein: the container has a nonporous bottom.
 25. A thermal transfer system as in claim 1 wherein: the container has nonporous walls.
 26. A thermal transfer system as in claim 1 wherein: the container has a top.
 27. A thermal transfer system as in claim 1 wherein: the container has a nonporous top.
 28. A thermal transfer system as in claim 1 including: a distal portion of the structure configured to improve thermal transport of the thermal transfer bridge.
 29. A thermal transfer system as in claim 1 wherein: the medium includes protiens.
 30. A thermal transfer system comprising: a container for receiving a medium; a structure positioned in the container, a heat exchange member at least partially coupled to the structure and extending into the container wherein a distal end of the heat exchange member is placed in close proximity to an interior surface of the container to allow the formation of a thermal transfer bridge that conducts heat into and out of the medium.
 31. A thermal transfer system as in claim 30 wherein: a heating or cooling device is coupled to and provides heating or cooling of the container.
 32. A thermal transfer system as in claim 30 wherein: a heating or cooling device is coupled to and provides heating or cooling of the structure positioned inside the container.
 33. A thermal transfer system as in claim 30 wherein: a heating or cooling device is coupled to and provides heating or cooling of the structure and the container.
 34. A thermal transfer system as in claim 30 wherein: there is a plurality of heat exchange members.
 35. A thermal transfer system as in claim 30, further comprising: a removable liner configured to cover at least a portion of the heat exchange member.
 36. A thermal transfer system as in claim 30 wherein: a volume of the container is in the range from substantially 1 liter to 250 liters.
 37. A thermal transfer system as in claim 30 wherein: a volume of the container is in the range from substantially 250 liter to 10,000 liters.
 38. A thermal transfer system as in claim 30 wherein: the container includes a jacket defining an interstitial space positioned between the jacket and a wall of the container for receiving a flow of a heat exchange fluid, the jacket further including a plurality of spiral baffles for enhancing thermal exchange between the heat exchange fluid and the container.
 39. A thermal transfer system as in claim 30 wherein: a heat exchange fluid flows within the structure.
 40. A thermal transfer system as in claim 30 wherein: the heat exchange fluid flows into the structure through an interior passage in the structure.
 41. A thermal transfer system as in claim 30 wherein: the heat exchange fluid flows out of the structure through an outer passage in the structure wherein one portion of the outer passage comprises an outer wall of the structure.
 42. A thermal transfer system as in claim 30 wherein: a heat exchange fluid flows within the heat exchange member.
 43. A thermal transfer system as in claim 39 wherein: an interior portion of the structure has baffles.
 44. A thermal transfer system as in claim 42 wherein: an interior portion of the heat exchange member has baffles.
 45. A thermal transfer system as in claim 39 wherein: an interior portion of the portion of the structure extending into the container has baffles.
 46. A thermal transfer system as in claim 39 wherein: the heat exchange fluid flows into the heat exchange member from the structure.
 47. A thermal transfer system as in claim 30 wherein: a heat exchange fluid flows into the heat exchange member from a heat exchange supply line.
 48. A thermal transfer system as in claim 38 wherein: the heat exchange fluid flows does not flow through the distal end of the heat exchange member.
 49. A thermal transfer system as in claim 30 wherein: a distance between the distal end of the heat exchange member and the interior surface of the container is a non-contacting distance not greater than one inch.
 50. A thermal transfer system as in claim 30 wherein: the medium is substantially uniformly heated or cooled.
 51. A thermal transfer system as in claim 30 wherein: the medium is heated or cooled in substantially one direction relative to the structure.
 52. A thermal transfer system as in claim 30 wherein: the medium is heated or cooled at a predetermined rate.
 53. A thermal transfer system as in claim 30 wherein: the medium is heated or cooled such that the thermal gradient is in a predetermined direction and the heating or cooling occurs at a predetermined rate.
 54. A thermal transfer system as in claim 30 wherein: the medium is a biopharmaceutical product.
 55. A thermal transfer system as in claim 30 wherein: the medium includes protiens. 